Mastectomy and Immediate Breast Reconstruction with Pre-Pectoral or Sub-Pectoral Implant: Assessing Clinical Practice, Post-Surgical Outcomes, Patient’s Satisfaction and Cost

Immediate breast reconstruction (IBR) rates increase during last years and implant-based reconstruction was the most commonly performed procedure. We examined data collected over 25 months to assess complication rate, duration of surgery, patient’s satisfaction and cost, according to pre-pectoral or sub-pectoral implant-IBR. All patients who received an implant-IBR, from January 2020 to January 2022, were included. Results were compared between pre-pectoral and sub-pectoral implant-IBR in univariate and multivariate analysis. We performed 316 implant-IBR, 218 sub-pectoral and 98 (31%) pre-pectoral. Pre-pectoral implant-IBR was significantly associated with the year (2021: OR=12.08 and 2022: OR=76.6), the surgeons and type of mastectomy (SSM vs NSM: OR=0.377). Complications and complications Grade 2–3 rates were 12.9% and 10.1% for sub-pectoral implant-IBR respectively, without significant difference with pre-pectoral implant-IBR: 17.3% and 13.2%. Complications Grade 2–3 were significantly associated with age <50-years (OR=2.27), ASA-2 status (OR=3.63) and cup-size >C (OR=3.08), without difference between pre and sub-pectoral implant-IBR. Durations of surgery were significantly associated with cup-size C and >C (OR=1.72 and 2.80), with sentinel lymph-node biopsy and axillary dissection (OR=3.66 and 9.59) and with sub-pectoral implant-IBR (OR=2.088). Median hospitalization stay was 1 day, without difference between pre and sub-pectoral implant-IBR. Cost of surgery was significantly associated with cup-size > C (OR=2.216) and pre-pectoral implant-IBR (OR=8.02). Bad-medium satisfaction and IBR-failure were significantly associated with local recurrence (OR=8.820), post-mastectomy radiotherapy (OR=1.904) and sub-pectoral implant-IBR (OR=2.098). Conclusion: Complications were not different between pre and sub-pectoral implant-IBR. Pre-pectoral implant-IBR seems a reliable and faster technique with better patient satisfaction but with higher cost.


Introduction
Total mastectomies for breast cancer (BC) are still indicated for 12 to 30% of patients and up to 40% [1][2][3][4][5]. It was 12.2% in a large French cohort of invasive BC and mastectomy rate increased according to four successive periods from 6.1% to 23.2% [6]. For risk reducing mastectomy, unilateral or bilateral mastectomies are indicated for BRCA mutations and for patients without BRCA mutation with estimated-risk of BC up to 25%. Immediate breast reconstruction (IBR) rates increase during the last years [7] in order to improve quality of life [8] and implant-based reconstruction was the most commonly performed procedure [9][10][11]. In our center, among 2112 mastectomies performed between January 2016 and July 2020, IBR-rate was 40.5%: 35.4% (618/1748) for primary BC, 47.9% (105/219) for local recurrence and 91% (132/145) for prophylactic mastectomies. Several new procedures are been developed, as robotic procedures [12][13][14][15], pre-pectoral implant-IBR with or without synthetic or acellular dermal matrix [7,[16][17][18][19][20][21]. However, it was reported that use of meshes significantly increases the cost of surgery [16]. Moreover, in recent year's nipple sparing mastectomy (NSM) is more and more frequently performed for prophylactic mastectomies [17], for local recurrence [18] and for primary BC [19,20]. Generally, the NSM studies reported better aesthetic results than skin-sparing mastectomy (SSM) and better quality of life [22][23][24]. NSM with IBR is consider today as a valid procedure for prophylactic mastectomy [17,[25][26][27][28] and an acceptable option for BC therapeutic mastectomy [29][30][31]. Complication rates varies between 5% and 61% in literature [32]. This wide difference in complications rates is explained by the difficulty of comparing the results of different studies due to the large disparities in IBR rates and techniques, the complications reported, the indications for mastectomies and the monitoring time. However, increased body mass index (BMI) and smoking were reported factors to increase the risk of complications as well as previous radiotherapy and operative time [21]. In this study, we report our experience at the Paoli Calmettes Institute, by analyzing the data collected over 25 months from January 2020 to January 2022 to assess clinical practice, complication rate, duration of surgery, patient's satisfaction and cost, according to pre-pectoral or sub-pectoral implant-IBR.

Methods
All patients who received an implant-IBR, from January 2020 to January 2022, were included, regardless of the indication for mastectomy from institutional database (study: M-IBR-PPRP-IPC 2022-014). The main characteristics were collected prospectively: year of IBR, use of matrix, type of mastectomy (NSM, SSM, or standard) and indication, associated axillary procedure, neo-adjuvant chemotherapy, age, duration of surgery, mastectomy weight, implant size, history of radiotherapy, ASA status (American Society of Anesthesiologists), smoking status, BMI and surgeon. Analyses were realized on all mastectomies, including two mastectomies for patients with bilateral procedures. Duration of anesthesia for bilateral mastectomies were halved. These criteria were compared between the two pre-pectoral and sub-pectoral prosthesis groups in univariate analysis and logistic regression. The following were analyzed: factors associated with the indication of IBR type, complications appeared in 90 days following the operation and grade 2-3 complications (Clavien Dindo classification), duration of surgery, and type of incision. The operative time was recorded from skin incision to skin closure. The choice between the two techniques was made by the surgeon and the matrices used were resorbable synthetic mesh TIGR Matrix ® (Novus Scientific, Uppsala, Sweden). The length of postoperative stay (LPOS) was reported from the surgery day to the discharge day from hospital. A loco regional anesthesia with pectoralis block was systematically perform. Costs of initial procedures were evaluated with costs addition of implant (400 Euros), number of hospitalization days (1495.69 Euros per day), duration of anesthesia (402.54 Euros per hour) and matrix TIGR (1390 Euros for 20×30 centimeters). Patient's satisfaction were evaluated as bad, medium, good and very good for patients without re-operation with implant loss for complication.

Statistics
Quantitative criteria were analyze with median, mean, 95% CI. Comparisons were determined using the Chi-2 test for qualitative criteria and t-test for quantitative criteria. Factors significantly associated with criteria analyzed were determine by a binary logistic regression adjusted for all significant variables identified by the univariate analysis. An odds ratio (OR) with a 95% confidence interval (95% CI) was used as an effective measure.
Statistical significance was assessed at p < 0.05. Analyses were perform with SPSS version 16.0 (SPSS Inc., Chicago, Illinois).

Pre or sub pectoral implant-IBR
Characteristics of patients according to pre or sub pectoral implant-IBR are reported in table 1. Bilateral mastectomy was performed in 48 patients: 29 in sub-pectoral group and 19 in pre-pectoral group. In univariate analysis, pre-pectoral implant IBR was significantly associated with years, NSM, axillary surgery type, neo-adjuvant chemotherapy, surgeon and age. There was no significant difference for mastectomy weight, histology, indication of mastectomy, breast size, smokers, ASA status, previous homo-lateral breast surgery, radiotherapy.
Pre or sub pectoral implant-IBR rates according to year of surgery and surgeons are reported in table 2. A great increase of pre-pectoral implant-IBR rate was observed for the four surgeons who realized pre-pectoral implant-IBR.
An IBR by pre-pectoral prosthesis was significantly associated with the year (2021: OR=12.08 and 2022: OR=76.6), the surgeons and the type of mastectomy (SSM vs NSM: OR=0.377) ( Table 3).
Incisions used for NSM were localized in breast inferior fold in the majority of patients (91%: 61/67) ( Table 4).
Complication type according to pre or sub-pectoral implant-IBR are reported in table 6, there was no significant difference (p=0.301). Implant loss rates were not significantly different: 6.40% and 9.20% for retro and pre-pectoral implant-IBR, respectively.
In multivariate analysis, complications were significantly associated with age <50 years (OR=2.0) and complications Grade 2-3 were significantly associated with age <50 years (OR=2.27) and ASA 2 status (OR=3.63) and breast cup-size >C (OR=3.08), without difference between pre and sub pectoral implant-IBR ( Table 7).

Duration of surgery
Median duration of surgery was 90.5 minutes (mean 97.1, CI95% 93.7-100.5), significantly higher for sub-pectoral implant-IBR in comparison with pre-pectoral implant-IBR: 100 minutes versus 80 minutes, p<0.0001. In multivariate analysis, medians duration of surgery higher than median value were significantly associated with breast cup size C and >C (OR=1.72 and 2.80, respectively), with sentinel lymph node biopsy and axillary lymph node dissection (OR=3.66 and 9.59, respectively), and with sub-pectoral implant-IBR (OR=2.088) in comparison with pre-pectoral implant-IBR ( Table 8).

Discussion
We report in this retrospective monocentric study an important number of patients with implant-IBR, during a recent and short period, with a high rate of IBR. Pre-pectoral implant-IBR were performed significantly more frequently for NSM. In multivariate analysis, complications Grade 2-3 were significantly associated with age <50 years, ASA 2 status and breast cup-size >C, without difference between pre and sub pectoral implant-IBR. Shorter duration of surgery was reported for pre-pectoral implant-IBR. A high rate of IBR reflects a relatively poor selection of patients for whom reconstruction is proposed. Conversely, a low rate of IBR is most likely related to a large selection of patients in whom an IBR is proposed. This can induce evaluation biases, particularly on complications rate, the patients most at risk having been excluded. In our practice, an IBR has been very widely proposed by excluding patients at very high risk of complication, or patients whose choice was not to perform an IBR. Patients considered to be at very high risk correspond to patients with significant sequelae from previous radiotherapy, or patients with significant and/or multiple co-morbidities. Inflammatory BC was also excluded to IBR. In this study, IBR rate was 38.5% which is relatively high and much higher than reported in the literature. Despite the COVID-19 pandemic, and a decrease in surgeries during this period having included several outbreaks, the number of surgeries for BC and the IBR rate were high [33,34]. The IBR rate in France was therefore assess at 16.1% in an observational study between 2008 and 2014 among 140,904 women who had undergone a total mastectomy for BC [7]. In England, the number of implant-IBR have increased since 2009: 10.0% until 2005 and 23.3% by 2013-2014 [9]. In Chinese, IBR rate was 9.6% (1,554/16,187) in year 2018, with implant or expander in 76.6% of these IBR [11]. However, the average rate of reconstruction in the United States in 2010 was 45%, surging to 54% in 2015 [35]. In the UK multicenter prospective cohort study [21], 2108 patients had 2655 mastectomies with implant-IBR in 81 units during 28 months: 11 patients' per-year per unit in comparison with 152 implant-IBR patient's per-year in this study. Moreover, Wow et al. [36] recently reported 232 implant-IBR with definitive implant or expander in two centers during 31 months (45 patients per-year per-center) including 123 risk-reducing mastectomy (53.0%) and a low rate of implant-IBR for BC (109 patients: 47%). In our study 85.8% of implant-IBR was performed for BC. IBR and NSM is possible for patients with ipsilateral local recurrence after initial conservative surgery with radiotherapy for BC in selective cases as we reported [18]. Pre-pectoral implant-IBR significantly increase according to years of treatment (6.0% to 72.7%) similarly to results reported by King et al. [37] (0% to 92.4%). Implant-IBR rate and type of mastectomy: pre-pectoral implant-IBR was performed less frequently for SSM than NSM, in Wow et al., study [36] (10.6% versus 81.6%, respectively) as we report (18.4% versus 45.9%). It is difficult to compared absolute complications rates between studies, due to a large disparity of IBR types, reported complications, indications for mastectomies, and monitoring time. Complication rates with pre-pectoral versus sub-pectoral implant-IBR were similar in meta-analysis reported by Li et al [38] and in meta-analysis reported by Chatterjee et al [39], but with lower odds of infection for pre-pectoral implant-IBR, and with higher rate of smokers, PMRT and diabetes in sub-pectoral procedures. Minor complications occurred more often for sub-pectoral procedures in Wow et al [36] study (26.32% versus 5.77%). In contrast, we don't report difference (2.76% versus 4.08%) like Momeni et al [40] (30% for pre-pectoral and 22.5% for sub-pectoral). We don't observe difference of major complications rates between pre and sub-pectoral implant-IBR like others, 10.9% pre versus 9.21% sub pectoral [36]. However, Momeni et al [40] reported higher major complication rate for sub-pectoral procedure (22.5% versus 7.5%) without significant difference (p=0.060). Significant higher prosthetic failure rate was reported for sub-pectoral versus pre-pectoral in King et al study [37] (18.7% versus 7.9%), but without significant difference in Momeni et al study [40] (2.5 versus 12.5% for pre and sub-pectoral implant IBR respectively), in meta-analysis reported by Chatterjee [39] and meta-analysis reported by Li et al [38], and without difference in the present study. A significant shorter median hospitalization time for pre-pectoral implant-IBR was reported by Wow et al [36], with a median time of 4 days for all patients. With a shorter median LPOS of 1 day, we don't observe difference between pre and sub-pectoral implant-IBR. Consequently, despite a shorter duration of anesthesia for pre-pectoral implant-IBR, we reported higher cost for pre-pectoral implant-IBR in comparison with sub-pectoral implant-IBR, as reported by Chopra et al [16]. Significant lower postoperative pain have been reported in pre-pectoral implant-IBR whereas others reported that the pain scores were not significantly different, without conclusion in Li et al meta-analysis [38]. Moreover, there was no significance difference of quality of life between the pre-pectoral and sub-pectoral groups in Li et al meta-analysis [38].
Several limitations of this study can be underlined: 1) retrospective design, even if the data was collected prospectively, 2) mono-centric study, 3) cost evaluation of initial surgery without true medico-economic study, 4) patient's satisfaction: patient satisfaction remains subjective but represents the predominant evaluation factor in relation to the opinion of doctors.

Conclusion
Complications Grade 2-3 were significantly associated with age <50 years, ASA 2 status and breast cup-size >C, without difference between pre and sub pectoral implant-IBR. Despite a shorter duration of surgery, higher cost was observed for pre-pectoral implant-IBR. More patients achieved bad or medium satisfaction for local recurrence, with PMRT and for sub-pectoral implant-IBR. Pre-pectoral implant-IBR seems to correspond to a reliable, faster technique with equivalent results in terms of complications and better patient satisfaction. To confirm these results, a multicenter study is ongoing.       Abbreviations: NSM, nipple sparing mastectomy; SSM, skin sparing mastectomy; ASA, American Society of Anesthesiologists; BMI, body mass index; RTH, radiotherapy; BC, breast cancer; PMRT, post-mastectomy radiotherapy; NAC, neo-adjuvant chemotherapy; N-RTH, neo-adjuvant radiotherapy.